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ORIGINAL ARTICLE
Effect of creatine plus caffeine supplements on time to exhaustion
during an incremental maximum exercise
CHIA LUN LEE
1
, JUNG CHARNG LIN
2
, & CHING FENG CHENG
3
1
Department of Recreational Sports Management, Yu Da University, Chaochiao Township, Taiwan, ROC,
2
Graduate
Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan, ROC, and
3
Department of Athletic
Performance, National Taiwan Normal University, Taipei, Taiwan, ROC
Abstract
This study investigated the effects of acute caffeine ingestion following short-term creatine supplementation on an
incremental cycling to exhaustion task. Twelve active males performed the task under three conditions: baseline condition
(BASE, no ergogenic aid), creatine plus caffeine condition (CRE CAF), and creatine with placebo condition
(CREPLA). Following the establishment of BASE condition, participants were administered CRE CAF
(0.3 g×kg
1
×day
1
of creatine for 5 days followed by 6 mg×kg
1
of caffeine 1 h prior to testing) and CRE PLA
(0.3 g×kg
1
×day
1
of creatine for 5 days followed by 6 mg×kg
1
of placebo 1 h prior to testing) in a double-blind,
randomized crossover and counterbalancing protocol. No significant differences were observed in relative maximal oxygen
consumption (V
˙O
2max
) (51.795.5, 52.894.9 and 51.395.6 ml×kg
1
×min
1
for BASE, CRECAF and CRE PLA,
respectively; P0.05) and absolute V
˙O
2max
(3.690.4, 3.790.4 and 3.590.5 l×min
1
for BASE, CRE CAF and
CREPLA, respectively; P0.05). Blood samples indicated significantly higher blood lactate and glucose concentrations
in the CRE CAF among those in the BASE or CRE PLA condition during the test (PB0.05). The time to exhaustion
on a cycling ergometer was significantly longer for CRE CAF (1087.29123.9 s) compared with BASE (1009.2986.0 s)
or CREPLA (1040.3996.1 s). This study indicated that a single dose of caffeine following short-term creatine
supplementation did not hinder the creatinecaffeine interaction. In fact, it lengthened the time to exhaustion during an
incremental maximum exercise test. However, this regime might lead to the accumulation of lactate in the blood.
Keywords: Aerobic capacity, ergogenic aids, grade exercise test, perceived exertion
Introduction
One ergogenic effect of caffeine (CAF, trimethyl-
xanthine) on exercise performance is a significant
increase in time to exhaustion (Flinn, Gregory,
McNaughton, Tristram, & Davies, 1990; Graham
& Spriet, 1995; Jackman, Wendling, Friars, &
Graham, 1996) and an increase in time trial perfor-
mance (Anderson et al., 2000; Wiles, Coleman,
Tegerdine, & Swaine, 2006). However, a number
of studies have indicated that CAF does not sig-
nificantly improve graded exercise performance
(Dodd, Brooks, Powers, & Tulley, 1991; Powers,
Byrd, Tulley, & Callender, 1983).
One study reported that supplementation with
creatine monohydrate (CRE) can significantly in-
crease work in time trials during a kayak ergometer
test in elite athletes (McNaughton, Dalton, & Tarr,
1998). Another study observed an improvement in
work to exhaustion at various exercise intensities for
CRE trials resulting from an increase in aerobic
phosphorylation (Rico-Sanz & Mendez Marco,
2000). However, several other studies failed to con-
firm the contention that CRE loading improves long-
term, high-intensity exercise performance (Balsom,
Harridege, Soderlund, Sjodin, & Ekblom, 1993;
Engelhardt, Neumann, Berbalk, & Reuter, 1998;
Izquierdo, Ibanez, Gonzalez-Badillo., & Gorostiaga,
2002; Thompson et al., 1996).
Ingestion of CAF can stimulate the secretion of
epinephrine (Jackman et al., 1996), which facilitates
Correspondence: Ching Feng Cheng, National Taiwan Normal University, Department of Athletic Performance, No. 88, Sec. 4, Ting-
Zhou Rd., Wen-shan District Taipei 116 Taiwan. E-mail: andescheng@ntnu.edu.tw
European Journal of Sport Science, July 2012; 12(4): 338346
ISSN 1746-1391 print/ISSN 1536-7290 online #2012 European College of Sport Science
http://dx.doi.org/10.1080/17461391.2011.573578
Downloaded by [National Taiwan Normal University] at 17:13 05 September 2012
the uptake of exogenous creatine by muscle tissue,
increases the Na
,K
-adenosine triphosphatase
pump activity, and raises the level of Na
sarcolem-
mic gradient (Clausen, 1996). Vandenberghe et al.
(1996) suggested that intramuscular creatine trans-
porters and concentrations of phosphocreatine might
be increased by the influence of hormones (i.e.
catecholamine) (Snow & Murphy, 2001) and
Na
,K
-adenosine triphosphatase (Clausen &
Flatman, 1977).
For this reason, Vandenberghe et al. (1996)
measured the performance of a maximal isometric
contraction task following treatment with CRE
(0.5 g×kg
1
×day
1
) in combination with CAF (5
mg×kg
-1
×day
-1
) supplementation for 5 days. Vana-
koski, Kosunen, Meririnne and Seppala (1998)
examined the effects of a 45-minute cycling task at
65% maximum oxygen consumption (V
˙O
2max
) fol-
lowing 3 days of supplementation with CRE (7
mg×kg
1
×day
1
) and CAF (0.3 g×kg
1
×day
1
).
Hespel, Op’t Eijnde and Van Leemputte (2002)
tested the relaxation time during a task comprising
30 intermittent contractions of the quadriceps mus-
cles following ingestion of CRE for 4 days (0.5
g×kg
1
×day
1
) and CAF for 3 days (5
mg×kg
1
×day
1
). Although these studies did not
confirm any benefits to exercise performance from
CRE plus CAF, they showed that the ratio of
muscular phosphocreatine/adenosine triphosphate
(PCr/ATP), concentrations of PCr (Vandenberghe
et al., 1996), and pharmacokinetic parameters of
CRE were unaffected by concomitant administration
of oral CAF (Vanakoski et al., 1998).
Doherty, Smith, Davison and Hughes (2002)
showed that acute ingestion of CAF (5 mg×kg
1
)
after 6 days of CRE (0.3 g×kg
1
×day
1
) supplemen-
tation with abstinence from CAF had an ergogenic
effect on running time to exhaustion (10.7% greater
than placebo trial) during a test of maximal accu-
mulated oxygen deficit, with exercise intensity
equivalent to 125% V
˙O
2max
. Interestingly, they
demonstrated that short-term, super high-intensity
exercise performance was improved following CAF
plus CRE loading on separate days. As yet, there has
been no clear explanation as to the means by which
CAF plus CRE influences physiological mechanisms
or endurance in tests such as an incremental max-
imum exercise test (IMET).
The primary purpose of this study was to determine
the effects of acute ingestion of CAF following short-
term oral CRE supplementation with abstinence from
CAF, as it relates to time to exhaustion during an
incremental maximum cycling test. The secondary
purpose was to investigate the effects of CRE plus
CAF on physiological responses, such as respiratory
and biochemical parameters. We hypothesize that
supplementation with CRE for 5 days prior to acute
CAF ingestion on the sixth day could improve time to
exhaustion during an IMET and increase metabolic
energy. Additionally, short-term CRE loading prior to
acute placebo ingestion is suggested to have a
negligible effect on cycling to volitional exhaustion.
Methods
Participants
Twelve males (age 2091.8 years, height 174.794.6
cm, body mass 69.1095.30 kg) studying at the
Department of Physical Education in the National
Taiwan Normal University were recruited for this
experiment, which was approved by the university’s
Human Research Ethics Committee. Before the first
trial, all participants completed a health-screening
questionnaire, signed a written informed consent
form, and answered questions regarding medical
history and the use of ergogenic aids. Results
indicated that they had not taken any medicine
within the previous three months and the volume
of CAF ingested was less than 50 ppm ×day
1
. All
participants were required to abstain from ingesting
any medication, caffeine and alcohol during the
study. All participants maintained regular physical
activity, but were asked to abstain from intense
exercise for 24 hours and fast for at least 4 hours
prior to visits to the laboratory. This reduced
any interference from exercise or food on the
experiment.
Experimental design
A double blind, randomized crossover and counter-
balancing experimental design was used. Each
participant visited the laboratory four times. During
the first visit, all participants were familiarized with
the cycling devices and protocol. All volunteers
participated in a practice session. During the
second visit, the baseline condition (BASE) was
established: an incremental cycling performance
test without any ergogenic aids. The participants
ingested CRE supplements for 5 days prior to the
third and fourth visits. On the sixth day, one hour
before the incremental cycling performance test,
each participant was administered either caffeine
(CRECAF) or a placebo (CRE PLA). The
third and fourth visits were separated by one month
to clear their systems of CRE as suggested by
Hultman, Soderlund, Timmons, Cederblad and
Greenhaff (1996).
Exercise procedure
After the participants arrived at the laboratory, their
body weight was measured and each individual was
Effect of creatine and caffeine on time to exhaustion 339
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administered capsules of either CAF or the placebo.
After one hour, the participants began the test with a
standardized warm-up procedure of a 5-minute sub-
maximal cycling at 50 W and a brief stretching exercise
for the lower legs and ankles. Each participant initially
pedaled at a work rate of 50 W on a cycling ergometer
(Avantronic Cyclus II, h/p Cosmos
†
, Germany). Every
2 minutes, the load was increased by 30 W. Cardio-
pulmonary responses were measured during the IMET
using a portable cardiopulmonary indirect breath-by-
breath calorimetry system (MetaMax 3B, Cortex Bio-
physik, Leipzig, Germany). Three of the following five
criteria (McConnell, 1988) had to be met to ensure that
each participant attained maximal effort: (1) heart rate
within 10 bpm of predicted maximum; (2) plateau of
oxygen uptake (V
˙O
2
) defined as no change (B150
ml×min
1
)inV
˙O
2
from the previous test stage; (3)
respiratory exchange ratio (RER) 1.1; (4) ventilation
volume 100 l ×min
1
; and (5) a Borg rating of
perceivedexertion(RPE)17 on the 620 scale.
V
˙O
2
, heart rate (HR), RER and RPE were analysed
throughout the duration of the test. A Polar heart rate
monitor (Polar S810i
TM
,PolarElectroInc.,Finland)
measured the HR during testing. The Borg RPE was
measured immediately after each sprint, with a rating of
6 indicating ‘‘no exertion’’ and 20 indicating ‘‘maximal’’
exhaustion.
Supplementation
During the second visit, the participants repeated
IMET, however they did so without CRE or CAF
supplements. Two days after the second visit, the
participants ingested 0.3 g ×kg
1
×day
1
of CRE
(Phosphagen HP
TM
, EAS, Golden, CO) per day
for 5 days. They were instructed to mix the CRE
powder in warm water (250 ml) for better dissolu-
tion (Harris, Soderlund, & Hultman, 1992) and to
ingest the solution with food in the morning, mid-
day, afternoon, and evening. This method of supple-
menting CRE is effective for increasing muscle
creatine content in young males (Harris et al.,
1992; Preen et al., 2001). During these five days,
the participants were required to abstain from
beverages/foods containing caffeine, as suggested
by Doherty et al. (2002). Upon arrival at the
laboratory, the participants were provided with
either 6 mg×kg
1
of CAF (Sigma-Aldrich, Sydney,
Australia) or an equivalent volume of a placebo
(maltodextrin; Starmax Nutrition, Hereford, UK) 1
hour prior to testing. Previous studies (Anselme,
Collomp, Mercier, Ahma
¨idi, & Prefaut, 1992; Spriet
et al., 1992) showed that the ingestion of this dosage
of CAF can elicit a positive ergogenic effect without
any serious side effects.
Blood sampling and analysis
During each trial, approximately 12 ml of blood was
taken from the antecubital vein via standard vene-
puncture techniques. Blood samples were drawn at
rest (prior to ingestion of supplements and exercise
testing, pre-test), 1 hour after ingesting the CAF or
placebo (post-ingestion), and after the incremental
maximum cycling test (post-test). Blood (8 ml)
containing ethylenediaminetetraacetic acid (EDTA)
was centrifuged at 3000 rpm for 15 minutes and
stored at 288C before immediate analysis of the
plasma for concentrations of epinephrine (Ep)
and norepinephrine (NEp) via high performance
liquid chromatography (HPLC) LCL 300
(Chromsystems
†
, Munchen, Germany), following
the method of Hue et al. (2000). The remaining
blood sample (4 ml) was centrifuged directly for
15 minutes and stored at 858C for analysis of
serum free fatty acid (FFA) with an automated clinical
chemistry analyser (model TBA-200 FR, Toshiba,
Tokyo, Japan). Capillary blood samples (10 ml) were
taken from the earlobe of each participant at pre-test,
immediately after each stage, and after the IMET (post-
test). A Biosen C-Line Sport Analyser (EKF Diagnos-
tics, Magdeburg, Germany) was used to analyse the
blood for lactate and glucose concentrations.
Statistical analysis
A one-way ANOVA with repeated measures (SPSS
for Windows 11.0, SPSS, Inc., Chicago, IL, USA)
was used to determine the effects of CRE plus CAF
supplementation on time to exhaustion, physiologi-
cal responses, and blood samples. When a significant
F-value was achieved, pairwise comparisons were
performed using a Bonferroni post hoc procedure.
Intraclass correlation coefficients were computed to
assess the consistency or testretest reliability of the
three trials. The obtained coefficients were signifi-
cantly moderate to high (from 0.48 to 0.98) in all
physiological variables tested. This statistical ap-
proach was selected because the purpose of the
study was to compare the effects of these supple-
ments on the three trials, not with the factor of time.
The change in FFA, Ep and NEp levels during post-
ingestion was calculated and compared for the trials
of CRECAF and CRE PLA using a two-tailed
paired sample t-test. Statistical significance was set at
P50.05 in all cases. Data were expressed as
mean9standard deviation.
Results
Physical characteristics
Body mass showed no significant difference among
the BASE, CRECAF, and CREPLA conditions
340 Chia Lun Lee et al.
Downloaded by [National Taiwan Normal University] at 17:13 05 September 2012
(BASE 69.1095.30 kg; CRECAF 69.9295.35
kg; CREPLA 69.7895.69 kg; P0.05). Follow-
ing ingestion of CAF capsules and the completion of
the test, two participants experienced a transient,
mild sense of anxiety, and one participant experi-
enced a slight stomachache.
Performance and physiological responses
Exercise time to exhaustion is shown in Figure 1.
The CRECAF condition achieved increases of
78.0 s and 46.9 s during IMET (F8.84, PB0.05),
compared with the BASE and CREPLA condi-
tions. No significant differences were noted with
regard to time to exhaustion during IMET between
BASE and CREPLA. Additionally, absolute
V
˙O
2max
(F1.58) and relative V
˙O
2max
(F0.83)
were not significantly different between BASE,
CRECAF, and CREPLA. Maximal HR in
CRECAF was significantly higher than in BASE
or CREPLA (F13.82), but no significant dif-
ference was observed between BASE and CRE
PLA (Table I).
Because all participants completed a workload of
230 W and were exhausted after at least 60 s under a
workload of 230 W, the differences in V
˙O
2
, HR,
RER and RPE were analysed for each 30 W interval
between 50 and 230 W. No significant effects of
supplementation on V
˙O
2
, HR and RER were found
between 50 W and 230 W load among the three
conditions, but the RPE at 230 W was significantly
lower in CRECAF than in the BASE or CRE
PLA (F7.28) (Table II).
Blood parameters
Figures 2, 3 and 4 illustrate the blood parameters. At
pre-test, no significant differences in blood glucose
or blood lactate concentrations were observed for
BASE, CRECAF and CRE PLA. During ex-
ercise, blood glucose was significantly increased in
CRECAF compared to BASE and CRE PLA at
each stage (Figure 2A). The concentration of blood
lactate in CRECAF was significantly higher than
in the CREPLA condition between 50 and 170 W
(Figure 2B).
At the time of exhaustion, CRECAF resulted in
significantly higher concentration of blood glucose
compared to BASE or CRE PLA; however, no
difference was observed between CRE PLA and
BASE (4.890.7, 6.090.7 and 5.190.5 mmol×l
1
for BASE, CRECAF and CRE PLA, respec-
tively). Additionally, the blood lactate in the
CRECAF condition at post-test was significantly
higher than that in the BASE or CREPLA conditions,
andthebloodlactatewassignificantlyincreasedinthe
CREPLA condition at post-test (9.791.9, 11.992.3
and 10.891.8 mmol×l
1
for BASE, CRECAF and
CREPLA, respectively; PB0.05).
A significant increase of 0.51 mmol ×l
1
in serum
FFA was observed in CRE CAF relative to
CREPLA at post-ingestion but not at pre-test or
post-test (Figure 3). No significant difference was
observed in serum FFA during the pre-test and post-
test among the BASE, CRECAF or CRE PLA
conditions (P0.05). Figure 4 shows that no
significant difference was observed between
CRECAF and CRE PLA in either plasma Ep
or NEp at any time. In addition, no significant
difference was noted in the level of plasma Ep or
NEp between the BASE, CRECAF or CRE
PLA conditions at pre-test or post-test (P0.05).
Discussion
This study was the first to examine the acute effects
of a single dose of CAF following short-term CRE
supplementation on time to exhaustion during an
incremental maximum cycling test. The results of
900
950
1000
1050
1100
1150
1200
1250
1300
Exercisetimetoexhaustion (sec)
BASE CRE+CAF CRE+PLA
*
†
Figure 1. Differences in time to exhaustion during an incremental
maximum cycling test for BASE, CRE CAF and CRE PLA.
$Significantly different to CRE PLA (PB0.05). *Significantly
different to baseline (PB0.05). Error bars indicate standard
deviation.
Table I. Maximal oxygen consumption (V
˙O
2max
) and maximal heart rate (HR
max
) in the three trials during the incremental maximum
cycling test.
Variable BASE CRE CAF CRE PLA
V
˙O
2max
(ml×kg
1
×min
1
) 51.795.5 52.894.9 51.395.6
V
˙O
2max
(l×min
1
) 3.690.4 3.790.4 3.590.5
HR
max
(bpm) 18798 19297* 18596
*Significantly different from BASE and CRE PLA (p B0.05). Values are mean9standard deviation.
Effect of creatine and caffeine on time to exhaustion 341
Downloaded by [National Taiwan Normal University] at 17:13 05 September 2012
Table II. Oxygen uptake (V
˙O
2
), heart rate (HR), respiratory exchange ratio (RER), rating of perceived exertion (RPE) in the three trials during different work rates.
Variable 50 W 80 W 110 W 140 W 170 W 200 W 230 W
V
˙O
2
(ml×kg
1
×min
1
)
BASE 17.39 92.35 19.48 92.11 22.93 92.57 27.47 92.81 33.14 93.11 38.54 93.77 44.02 94.42
CRE CAF 17.08 91.98 18.66 91.91 22.08 91.87 26.83 92.11 32.31 93.08 37.16 93.06 42.52 93.40
CRE PLA 17.70 91.71 19.39 91.63 22.75 91.58 27.58 91.88 32.62 92.43 37.75 92.56 43.19 93.04
V
˙O
2
(l×min
1
)
BASE 1.19 90.11 1.33 90.10 1.57 90.11 1.88 90.13 2.27 90.15 2.64 90.17 3.02 90.22
CRE CAF 1.17 90.06 1.28 90.07 1.53 90.08 1.86 90.09 2.24 90.10 2.57 90.14 2.95 90.13
CRE PLA 1.23 90.10 1.34 90.09 1.57 90.09 1.90 90.09 2.26 90.13 2.61 90.12 2.98 90.16
HR (bpm)
BASE 105 911 109 911 119 911 132 911 144 911 157 912 168 911
CRE CAF 104 913 109 914 118 914 130 914 144 915 157 914 170 912
CRE PLA 107 910 111 99 122 99 134 99 146 99 157 98 167 98
RER
BASE 0.73 90.69 0.78 90.06 0.82 90.07 0.86 90.08 0.90 90.08 0.96 90.07 1.02 90.08
CRE CAF 0.75 90.05 0.82 90.06 0.86 90.06 0.89 90.08 0.94 90.07 0.98 90.07 1.04 90.93
CRE PLA 0.74 90.07 0.80 90.04 0.83 90.04 0.87 90.04 0.91 90.04 0.95 90.05 1.01 90.07
RPE
BASE 7 9189110921192129314931692
CRE CAF 8 9199210921192139214921592*
CRE PLA 8 9199211921292149215921792
*Significantly different from BASE and CRE PLA (PB0.05). Values are mean9standard deviation.
342 Chia Lun Lee et al.
Downloaded by [National Taiwan Normal University] at 17:13 05 September 2012
the study showed that five days of CRE loading (0.3
g×kg
1
×day
1
) before a single dose of CAF (6
mg×kg
1
) increased IMET performance, blood
lactate, blood glucose and FFA concentrations, but
did not influence maximum oxygen consumption,
heart rate, RER or catecholamines.
Vanakoski et al. (1998) observed no difference in
heart rate between individuals taking CRE CAF
and those taking CRE during a 45-minute exercise at
constant 65% V
˙O
2max
. However, they did not
examine endurance or oxygen consumption during
the test. This study showed that average time to
exhaustion during an IMET with CRE CAF was
greater than that achieved with CRE PLA (4.51%
increase) or BASE (7.73% increase). Therefore, this
study determined that short-term loading of CRE
before acute ingestion of CAF can extend time to
exhaustion during an incremental maximum cycling
test. Supplementation with CRE can help to increase
total muscular concentrations of creatine and PCr
resynthesis (Greenhaff, Bodin, Soderlund, & Hult-
man, 1994; Hultman et al., 1996). The operation of
intracellular Ca
2
improved (Pulido et al., 1998) to
augment the availability of PCr for active sarcoplas-
mic reticulum (SR)-bound creatine kinase, increas-
ing the local supply of ATP to the SR-Ca
2
pump
(O’Gorman et al., 1997) and levels of creatine
transporter (Snow & Murphy, 2001). This could
be the explanation for the benefits of CRE.
Supplementation with CREPLA did not en-
hance long-term aerobic exercise performance in
either our study or previous studies. The ergogenic
potential of supplementation with CRE in endurance
performance has typically yielded either non-signifi-
cant results in the endurance of well-trained athletes
(Engelhardt et al., 1998; Izquierdo et al., 2002;
Thompson et al., 1996) or a negative impact on
prolonged, high-intensity endurance performance
(Balsom et al., 1993). This could be caused by
either a failure of CRE to enhance glycogen content
in muscle or an increase in body weight, which
retarded performance. Nevertheless, the present
study did not observe a significant increase in body
weight nor measure the glycogen content in the
muscles following supplementation with CRE
PLA or CRECAF. We suggest that further
studies could investigate this indistinct area.
Graham, Battram, Dela, El-Sohemy and Thong
(2008) found that concentrations of cyclic adenosine
monophosphate (cAMP) in muscles increased dur-
ing 7080% V
˙O
2max
exercise following acute inges-
tion of CAF. Thus, CAF probably acts directly on
0
2
4
6
8
10
Blood lactate (mmol • l–1)
BASE CRE+CAF CRE+PLA
†††††
0
2
4
6
8
10
Blood glucose (mmol • l–1)
BASE CRE+CAF CRE+PLA
(A)
(B)
*****
†
Pre-test 50 Watts 80 Watts 110 Watts 140 Watts170 Watts 200 Watts 230 Watts
††††††
**
Figure 2. Blood glucose (A) and lactate concentrations (B) at pre-test and each stage during an incremental maximum cycling test for
BASE, CRE CAF and CRE PLA. $Significantly different to CRE PLA (PB0.05). *Significantly different to baseline (PB0.05).
Error bars indicate standard deviation.
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Pre-test Post-in
g
estion Post-test
Serum free fatty acid (mmol • l–1)
CRE+CAF CRE+PLA
†
Figure 3. Ser um free fatty acid in CRE CAF and CRE PLA
at pre-test, post-ingestion and post-test. $Significantly different to
CRE PLA (PB0.05). Error bars indicate standard deviation.
Effect of creatine and caffeine on time to exhaustion 343
Downloaded by [National Taiwan Normal University] at 17:13 05 September 2012
ryanodine receptors to release potential Ca
2
from
skeletal muscle SR. Additionally, an increase in time
to exhaustion might be explained by the participants
feeling a reduction in discomfort (Plaskett &
Cafarelli, 2001) or muscular pain (Motl, O’Connor,
& Dishman, 2003) following ingestion of CAF. Our
findings indicate that ingestion of CRE plus CAF
significantly reduces RPE at 230 W, while partici-
pants were close to exhaustion. These results concur
with Doherty et al. (2002). CAF may also improve
high-intensity endurance performance by increasing
the circulation of epinephrine or by sympathetic
stimulation (Graham & Spriet, 1995), thereby de-
creasing RPE during intense exercise (Doherty &
Smith, 2005).
No previous research has examined the effect of
CRE plus CAF on V
˙O
2
or heart rate during an
incremental maximum cycling test. Observation of
V
˙O
2
, HR and RER at each workload demonstrated
no significant difference between the BASE,
CRECAF and CRE PLA trials (Table II).
Physiological responses were similar to those ob-
tained in previous studies (Dodd et al., 1991;
Gaesser & Rich, 1985; Powers et al., 1983), demon-
strating that the ingestion of 5 or 7 mg×kg
-1
of CAF
did not alter oxygen consumption, HR or RER but
significantly increases the levels of FFA and lactate in
the blood. Although high concentrations of FFA
were induced by the ingestion of CAF (Dodd et al.,
1991; Gaesser & Rich, 1985; Powers et al., 1983;
Raguso, Coggan, Sidossis, Gastaldelli, & Wolfe,
1996), the data of RER during exercise and con-
centrations of FFA after exercise did not demon-
strate a caffeine-mediated glycogen sparing effect
secondary to an increased rate of lipolysis (Dodd et
al., 1991; Graham et al., 2008; Graham, Helge,
MacLean, Kiens, & Richter, 2000). Thus, our data
is in agreement with Graham et al. (2000, 2008),
showing no support for the effect of CAF on
increased fat oxidation or inhibition of carbohydrate
catabolism.
The significant increase in blood lactate and
concentration of glucose in CRE CAF compared
to BASE or CREPLA are likely due to a reduction
in blood lactate clearance (Graham et al., 2000) and
a decrease in the uptake of glucose by active muscles
(Raguso et al., 1996). Muscle biopsy analysis
showed that intramuscular cAMP increased at work-
load of 70% V
˙O
2max
following ingestion of CAF
(Graham et al., 2000). This may be in responses to
muscle glycogen and glycolytic flux (Chesley, How-
lett, Heigenhauser, Hultman, & Spriet, 1998).
Although glucose-6-phosphate tends to be higher
and concentrations of glycogen in the muscle tend to
be lower after exercising at 70% V
˙O
2max
during
treatment with CAF, the difference was not signifi-
cant between the CAF and placebo trials (Graham et
al., 2000). However, the concentration of glycogen
in the muscle was not measured in this study, and the
actual mechanism behind lactate and glucose follow-
ing supplementation with CRECAF requires
further study. So far, no good explanation has been
provided (Chesley et al., 1998; Graham et al., 2000)
to describe the action of CAF on lactate or glucose in
muscle. In addition, the present study showed no
significant differences between the trials with regard
to Ep and NEp. No significant difference was found
in catecholamine levels at any time between the
CRECAF and CRE PLA conditions. This
might be due to the fact that only a single dose of
CAF was used in this study. The CAF dose might
not have been strong enough to produce an ob-
servable difference between the CAF and the place-
bo. Interpreting the results of plasma Ep and NEp in
our study was difficult, due to the large variations
observed. Further study is needed to clarify the
relationship between caffeine-induced changes in
catecholamine, blood lactate, glucose and an incre-
mental cycling endurance performance.
A number of studies have suggested that ingesting
caffeine in conjunction with creatine negates the
potential ergogenic value on the exercise perfor-
mance. The study clearly refutes these contentions
and uncovers a number of additive benefits. In
conclusion, five days of supplementation with CRE
with caffeine abstinence followed by the ingestion of
a single dose of caffeine one hour prior to exercise
improved time to exhaustion during an incremental
0
100
200
300
400
500
600
700
800
900
1000
Plasma epinephrine (pg • ml–1)
CRE+CAF CRE+PLA
0
200
400
600
800
1000
1200
1400
Pre-test Post-in
g
estion Post-test
Plasma norepinephrine (pg • ml–1)
CRE+CAF CRE+PLA
(B)
(A)
Figure 4. Plasma epinephrine (A) and norepinephrine (B) con-
centrations in CRE CAF and CRE PLA at pre-test, post-
ingestion and post-test. The plasma epinephrine and norepi-
nephrine concentrations are not significantly different between
CRE CAF and CRE PLA at every point (P0.05). Error
bars indicate standard deviation.
344 Chia Lun Lee et al.
Downloaded by [National Taiwan Normal University] at 17:13 05 September 2012
maximum cycling test and induced higher levels of
blood lactate and glucose throughout the test. In
practice, athletes who engage in high-intensity en-
durance exercise could benefit from the additive
effects of caffeine ingested after a short-term creatine
loading. However, the ingestion of caffeine results in
higher concentrations of blood lactate; therefore,
coaches and athletes should use this supplemental
strategy with caution.
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